Identifying the incidence of respiratory complications following diaphragmatic cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy.

INTRODUCTION: In patients with peritoneal carcinomatosis (PC), the incidence of respiratory complications following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is not well established. We aimed to describe the center-specific incidence and patient characteristics associated with respiratory complications following CRS and HIPEC in patients receiving treatment for PC. MATERIALS AND METHODS: We used the University Hospital of Arrixaca study database to identify patients who underwent CRS and HIPEC for PC. Patients who experienced a post-operative respiratory complication were categorized according to the National Cancer Institute-Common Terminology Criteria for Adverse Events. Multivariable regression methods were used to identify independent risk factors for developing a respiratory complication following CRS and HIPEC. RESULTS: Between 2008 and 2017, we identified 247 patients who underwent CRS and HIPEC for PC. A total of eight patients (3.2%) were categorized as having a post-operative respiratory complication. A diaphragmatic peritonectomy and a PC index of > 14 were identified as independent risk factors for developing a respiratory complication. Radiographic evidence of a pleural effusion was identified in 72 patients who had CRS of the diaphragmatic peritoneum; however, only 6 (8.3%) of these patients required pleural drainage. CONCLUSIONS: Only 3.2% of patients developed a symptomatic respiratory complication following CRS and HIPEC. A pleural effusion was identified in almost all patients requiring a diaphragmatic peritonectomy as part of their CRS; however, less than one in ten of these patients required pleural drainage. Prophylactic insertion of a pleural drainage tube is, therefore, not indicated following CRS and HIPEC.

Effect of Paclitaxel-based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on colonic anastomosis in a rat model.

BACKGROUND: Paclitaxel has been used frequently for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for ovarian carcinomatosis. Cytoreductive surgery and HIPEC are associated with high rates of morbidity being anastomotic dehiscence one of the most frequent. The objective of this study is to quantify the effect of Paclitaxel-based HIPEC on colonic anastomosis in an experimental rat model. METHODS: After left colon resection and anastomosis, animals were randomized into four groups: Controls (C); Hyperthermia (H); Normothermic Intraperitoneal Paclitaxel (CP) and Paclitaxel-based HIPEC (HP). On postoperative day four, animals' peritoneal cavities were examined macroscopically, colon anastomosis burst pressures measured and specimens analyzed histologically. RESULTS: Thirty-nine animals were randomized and 36 were included in the analysis. H group presented the highest burst pressure 105.11 ± 22.9 mmHg, which was 27% higher than C (77.89 ± 27.6 mmHg). On the other hand, HP presented the lowest burst pressure 64 ± 26 mmHg, 16% lower than C group and 39% lower than H, being this latter difference statistically significant (p = 0.004). There were no significant differences regarding weight loss, adhesion scores, perianastomotic abscesses and histological findings (inflammation, fibroblasts, neoangiogenesis, and collagen among groups). CONCLUSION: Strength of colonic anastomosis was improved by isolated hyperthermia and negatively affected by Paclitaxel-based HIPEC.

Presence of 236U and 239,240Pu in soils from Southern Hemisphere.

236U, 239Pu and 240Pu are present in soils mainly as a result of the local- and global-fallout from the atmospheric nuclear weapons tests carried out mainly in the 1950's and 1960's. In this work we provide new data on the presence of 236U and 239,240Pu in surface soils (i.e. up to 5 cm depth) from Chile and Africa. The results were obtained by low-energy Accelerator Mass Spectrometry (AMS). In the case of the Chilean samples, 236U/239Pu atom ratios show a high variability and are in general higher than the reported value for the global fallout in the Northern Hemisphere, ranging from 0.2 to 1.5. The 236U atomic concentrations range from 3.5 × 106 to 9.1 × 106 atoms/g, and are at least two orders of magnitude lower than the reported values in the Northern Hemisphere. The measured 240Pu/239Pu atom ratio in soils from South-Africa and Mozambique are of about 0.17, in agreement with the expected one for global-fallout at those coordinates. To best knowledge of the authors the present work is the first publication on 236U concentrations and 236U/239Pu atom ratios in soils from South-America and Africa.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei and appendix tumours in elderly patients: Is it justified?

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei and appendix tumours are widespread in the world. It is unclear what should be the attitude in elderly patients. METHODS: This retrospective multicenter study collected the database from ten Spanish centers from Spanish Group of Peritoneal Cancer Surgery. The study period was between November 2002 and March 2014. Seventeen patients with age greater than or equal to 75 years with peritoneal carcinomatosis from pseudomyxoma peritonei and appendix tumours met the selection criteria for the study. Outcomes in terms of morbidity and mortality such as disease-free and overall survival were analyzed. RESULTS: Median PCI was 16 (range 6-39). Ten postoperative adverse events were detected in nine patients (44.4%). 28% were grade I-II and 17% were grade III-IV. Disease-free survival at 1 and 3 years was 67 and 44%, respectively. Overall survival at 1 and 3 years was 100 and 88%, respectively. Only cytoreduction was related to worst disease free survival after univariate (p = 0.007) and multivariate (OR 11.639, 95% CI 1.24-109.74, p = 0.03) analyses. Cytoreduction was related to the worst overall survival after univariate analysis (p = 0.046). CONCLUSION: Cytoreductive surgery and HIPEC for pseudomyxoma peritonei and appendix tumours in elderly patients it is a procedure with feasible postoperative morbi-mortality and survival outcomes. TRIAL REGISTRATION: researchregistry1587 (retrospectively registered).

Effectiveness and failures of a fast track protocol after cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy in patients with peritoneal surface malignancies.

BACKGROUND: The aim of this study was to analyze the results short term perioperative of patients with peritoneal surface malignancies undergoing cytoreduction with peritonectomy and HIPEC under a controlled fast track protocol and evaluate the factors related to the failure of implementation of the protocol. PATIENTS AND METHOD: We prospectively analyzed a consecutive series of patients (N = 156) with peritoneal surface malignancies treated by cytoreductive surgery with peritonectomy procedures and HIPEC from September 2008 until December 2014, in whom a fast track protocol was implemented. We limited the protocol to patients who had optimal cytoreduction, HIPEC administration, and not more than one digestive anastomosis. All patients signed informed consent for surgery and the perioperative multimodal recovery program. RESULTS: A total of 156 consecutive patients, with a median age of 57 years were included in the study. Median PCI was 8 (IQR: 0-32). Morbidity rate (Clavien-Dindo) was 25.6%, with a major morbidity rate (Clavien-Dindo III-IV) of 11.5%. One hundred and three patients (66%) completed the protocol. Multivariate analysis identified the following independent factors, which were related to failure of the protocol: age over 57 years (OR = 3.159, 95% CI: 1.286-7.758, p < 0.05), the realization of a digestive anastomosis (OR = 3.834, 95% CI: 1.562-9.414, p < 0.005) and occurrence of postoperative complications (OR = 18.704, 95% CI: 6.888-50.790, p < 0.001) CONCLUSIONS: Our data support the idea that in selected patients undergoing cytoreductive surgery and HIPEC, with a low PCI and especially no necessity to perform a digestive anastomosis, the implementation of a fast track program is feasible.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in elderly patients. A systematic literature review.

The objective of this review was to evaluate morbidity, mortality and survival outcomes of elderly patients with peritoneal carcinomatosis. A systematic literature search and standardized data collection of primary research publications until June 2016 on morbidity, mortality and survival outcomes in adults aged 65 and older with peritoneal carcinomatosis treated with cytoreduction and HIPEC was performed, using PubMed, EMBASE, Scopus, ClinicalTrials.gov and Cochrane. Bibliographies of relevant reports were also hand-searched to identify all potentially eligible studies. Nine studies were included. Severe morbidity of all elderly patients ranges from 17% to 56% in centers with high experience. In-hospital and 30-day mortality ranges from 0% to 8%. In only two studies were the differences in morbidity and mortality statistically significant related to the control group. However, older adults undergoing cytoreductive surgery and HIPEC consistently had lower survival rates across all study settings and procedure types than younger individuals. In studies that stratified for elderly patients, PCI, completeness of cytoreduction, tumor histology and albumin levels were predictive factors of survival. None of these studies examined quality of life, which precludes including functional outcomes in this review. Differences in exposures, outcomes, and data presented in the studies did not allow for quantification of association using a meta analysis.

Hyperthermic intraperitoneal chemotherapy with paclitaxel or cisplatin in patients with stage III-C/IV ovarian cancer. Is there any difference?

OBJETIVE: To compare the results of the administration of HIPEC with Paclitaxel or Cisplatin after cytoreduction in patients with stage IIIC-IV ovarian cancer, especially focused on disease-free survival. PATIENTS: We retrospectively analyzed a consecutive series of patients operated after being diagnosed with stage III-C/IV serous epithelial ovarian carcinoma. Patients included in the study were treated between January 2008 and March 2015. After cytoreduction, Paclitaxel (doses of 60 mg/m(2)O or Cisplatin (doses of 75 mg/m(2)) were used. RESULTS: A total of 111 patients were included. Median age was 61 years. In 60 of them (54%) Paclitaxel was used during HIPEC treatment and 51 patients (46%) were treated with Cisplatin. PCI was similar between groups (PCI = 11 in both cases). Median follow up was 34 months (12-96 months). The median disease free survival in Paclitaxel Group was 27 months and 33 months in Cisplatin Group (p = 0.551). In patients treated with Paclitaxel disease free survival rates at 1, 2, and 3 years were 79%, 60% and 46%. In patients treated with Cisplatin disease free survival at 1, 2, and 3 years were 64%, 50% and 40% respectively. After a multivariate analysis, incomplete cytoreduction (HR: 6.54, 95% CI 2.98-10.17, p < 0.01) and PCI >11 (HR: 2.15, 95% CI 1.42-6.68, p < 0.05) were identified as independent factors associated with a reduced disease-free survival. Cystotatic used was not relevant regarding disease free survival analysis. CONCLUSION: HIPEC with paclitaxel or cisplatin after cytoreduction in patients with ovarian cancer IIIC-IV has not shown different results in disease-free survival outcomes.

Whole-blood fatty acids and inflammation in European children: the IDEFICS Study.

BACKGROUND/OBJECTIVES: Fatty acids are hypothesized to influence cardiovascular disease risk because of their effect on inflammation. The aim of this study is to assess the relationship between whole-blood fatty acids (WBFAs) and high-sensitivity C-reactive protein (hs-CRP) in European children. SUBJECTS/METHODS: A total of 1401 subjects (697 boys and 704 girls) aged between 2 and 9 years from the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects in Children and infantS) study were measured in this cross-sectional analysis. The sample was divided into three categories of hs-CRP. Associations between WBFA and hs-CRP were assessed by logistic regression models adjusting for body mass index (BMI), country, age, breastfeeding, mother's education and hours of physical activity. RESULTS: Linoleic acid (LA) (P=0.013, 95% confidence interval (CI): 0.822-0.977) and sum of n-6 WBFA (P=0.029, 95% CI: 0.866-0.992) concentrations were associated with lower concentrations of hs-CRP in boys. In girls, a high ratio of eicosapentaenoic acid (EPA)/arachidonic acid (AA) was associated (P=0.018, 95% CI: 0.892-0.989) with lower hs-CRP concentrations. In contrast, sum of blood n-6 highly unsaturated fatty acids (P=0.012, 95% CI: 1.031-1.284), AA (P=0.007, 95% CI: 1.053-1.395) and AA/LA ratio (P=0.005, 95% CI: 1.102-1.703) were associated (P<0.05) with higher concentrations of hs-CRP in girls. CONCLUSIONS: The n-6 WBFAs (sum of n-6 FA and LA) were associated with lower hs-CRP in boys and with higher hs-CRP in girls (AA, sum of n-6 highly unsaturated and AA/LA ratio). More studies are needed to identify the optimal levels of WBFAs to avoid low-grade inflammation in children considering the differences by sex and BMI.

The role of hyperthermic intraperitoneal chemotherapy using paclitaxel in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction.

BACKGROUND: We analyzed the role of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) on the microscopic component of the disease in patients with a first recurrence of platinum-sensitive ovarian cancer after complete cytoreduction (CCR). PATIENTS AND METHODS: We analyzed the data of 54 patients who were operated on between January 2001 and July 2012 with the diagnosis of platinum-sensitive recurrent ovarian cancer. In all patients, it was possible to achieve a CCR. Patients were divided into two groups: group I (cytoreduction alone) consisted of 22 surgical patients and group II (cytoreduction and HIPEC) consisted of 32 patients. RESULTS: There were no significant differences in any of the preoperative variables studied. After a multivariate analysis of factors identified in the univariate analysis, only the presence of tumors with undifferentiated histology (hazard ratio 2.57; 95% CI 1.21-5.46; p < 0.05) was an independent factor associated with a reduced disease-free survival. The 1- and 3-year disease-free survival was 77 and 23% in patients from group I and 77 and 45% in patients from group II, respectively, with a tendency, but no significant differences (p = 0.078). There was no significant difference in postoperative morbidity between the two groups. CONCLUSIONS: The administration of HIPEC in patients in whom it is possible to achieve a CCR of the disease has not increased postoperative morbidity and mortality rates in our center. HIPEC with paclitaxel is effective in the treatment of microscopic disease in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction, although with no statistically significant difference.

Treatment of microscopic disease with hyperthermic intraoperative intraperitoneal chemotherapy after complete cytoreduction improves disease-free survival in patients with stage IIIC/IV ovarian cancer.

BACKGROUND: We analyze the efficacy of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) for microscopic residual disease in patients with stage IIIC/IV ovarian cancer after a complete cytoreduction of their disease. PATIENTS AND METHODS: We analyzed the data of 87 consecutive patients diagnosed with stage IIIC/IV ovarian cancer operated between December 1998 and July 2011. In every patient it was possible to achieve a complete cytoreduction of their disease. (Since January 2008, our center has incorporated the use of HIPEC in patients with peritoneal surface malignancies, including patients with peritoneal dissemination of primary ovarian cancer.) RESULTS: Of 87 patients, 52 were treated with HIPEC (paclitaxel 60 mg/m(2), 60 min, 42 °C). After a univariate analysis, factors associated with lower disease-free interval were: performing a gastrointestinal anastomosis, operative time greater than 270 min, poorly differentiated histology, and not being treated with HIPEC. After multivariate analysis, independent prognostic factors included not being treated with HIPEC [hazard ratio (HR) 8.77, 95 % CI 2.76-14.42, p < 0.01] and the presence of poorly differentiated tumors (HR 1.98, 95 % CI 1.45-8.56, p < 0.05). Disease-free survival at 1 and 3 years was 66 and 18 %, respectively, in patients without HIPEC and 81 and 63 %, respectively, in patients treated with HIPEC (p < 0.01). HIPEC administration did not alter the results obtained for disease-free survival in patients with undifferentiated tumors. CONCLUSIONS: The treatment of the microscopic disease following complete cytoreduction with HIPEC in patients with advanced ovarian cancer is effective and can prolong disease-free survival. This survival benefit was not seen in undifferentiated tumors.

[The creation of a new nutritional market in Spain: vitamins in the press (1917-1950)]. / La creación de un nuevo mercado alimentario en España: las vitaminas en la prensa periódica (1917-1950).

AIM: To analyze the extent to which vitamins played a role in the strategy to create a new market of food, food-medicines, and medicines in Spain during the first half of the twentieth century. MATERIALS AND METHODS: A study was made of references to vitamins in the years between 1917 and 1950 in the daily newspapers "ABC", "Heraldo de Madrid", "El Imparcial", "El Liberal" and "El Sol", published in Madrid, "La Vanguardia", published in Barcelona, and the weekly publication "Blanco y Negro". The starting date was selected as the year in which the first news of vitamins appeared. The year 1950 marked the end of the harshest stage of autarky imposed by Franco's regime. The news that appeared was classified in the following categories: scientific news, nutritional advice, advertising, economy, politics, anecdotes and metaphors. RESULTS: The advertisements that used vitamins as part of their marketing strategy are the most important section with over 50% of total references to the vitamin concept in almost all the newspapers. Scientific news on vitamins ranks second in importance. References to vitamins in the remaining categories were below 5%. CONCLUSIONS: Judging by the references which appear in the most important newspapers of the time vitamins represent a fundamental element in the creation of a new food product market in Spain in the first half of the twentieth century.

Produtos naturais com potencial leishmanicida / Natural products with leishmanicide potential

A leishmaniose é uma parasitose causada porprotozoários do gênero Leishmania. É uma doença endêmica que abrange mais de 80 países, incluindo alguns do continente europeu e, principalmente, países sub-desenvolvidos ou em desenvolvimento. Nesta revisão discorre-se sobre as opções terapêuticas tradicionais e atuais, cuja atividade leishmanicida pode conduzirao desenvolvimento racional de novos fármacos. Ressaltando-se o uso de produtos naturais na pesquisa e tratamento de Leishmaniose (ex. quinolonas, chalconase extratos brutos).

Single restraint stress sensitizes acute chewing movements induced by haloperidol, but not if the 5-HT1A agonist 8-OH-DPAT is given prior to stress.

The objective of this study was two-fold: (i) to analyze behavioral sensitization to haloperidol 2 weeks after single restraint stress, and (ii) to establish the effects of 8-OH-DPAT treatment prior to stress on sensitized behavioral responses. Overall behavior was analyzed and not only catalepsy, but also sedation (immobility), grooming, exploration and vacuous chewing movements were evaluated. Results indicated that single restraint stress induced a long-lasting sensitization of acute vacuous chewing movements induced by haloperidol (0.25, 0.5 mg/kg i.p.). Interestingly, this behavioral sensitization was prevented by 8-OH-DPAT (0.35 mg/kg s.c.) prior to stress. Finally, haloperidol-induced sedation was not disrupted by either restraint stress or 8-OH-DPAT treatment.

[Clinical efficacy and tolerance to acarbose in the treatment of non-insulin-dependent diabetic patients]. / Eficacia clínica y tolerancia de la acarbosa en el tratamiento de pacientes diabéticos no dependientes de la insulina (tipo II).

BACKGROUND: Acarbose is a pseudotetrasacaride which reversibly and competitively inhibits the intestinal alpha-glycosidases leading to a decrease in the increase of postprandial glycemia. METHODS: A multicentric double-blind clinical trial (8 centers), controlled versus placebo, crossover and randomized was carried out in 90 non insulin dependent diabetic patients under treatment with diet or with diet and sulphonilureas. During the first three months of the trial the patients received placebo or acarbose randomly. Following one months of wash-out with placebo the patients received the inverse medication for 3 more months. During the first month of each phase the patients received 3 x 50 mg/day of acarbose or placebo and the following 2 months 3 x 100 mg/day. RESULTS: Upon comparison of the two treatments significant statistical differences were observed in HbA1 (p = 0.0115) and in postprandial glycemia (p = 0.0001). There were differences, although not significant, in the levels of triglycerides, cholesterol, fasting glycemia, and postprandial insulinemia. Episodes of hypoglycemia appeared in 12 patients and 57 patients referred undesirable gastrointestinal effects. CONCLUSIONS: The results of this trial indicate that acarbose may be useful in the treatment of non insulindependent diabetic patients since it significantly reduces the amount of postprandial glycemia and HbA1.